Cell Signaling

Classes of receptors

RTK

Cytokine

TGFB

Integrin

Hormone

GPCR

Receptor tyrosine kinases (RTKs)

protein kinase- removes high energy phosphate group from ATP and transfers it to a suitable protein substrate (phosphorylation)

Juxtracrine signaling

involves expression of ligand that remains tethered to ligand-presenting cells

ErbB oncoprotein

avian erythorblastosis virus (AEV) transforming retrovirus that rapidly induces leukemia in red blood cell precursors

lacks ectodomain- can’t bind its ligand

active independent of ligand

receptor mutations

mutations cause cancer cell receptors to mimic tyrosine kinases without having a ligand

gene fusion causing constitutively dimerized receptors

reading frame specifying the ectodomain of ROS gene gets fused to another gene (FIG) that encodes protein that dimerizes spontaneously

Cytokine function

Regulate cell growth and immune system

What type of receptor is TGFB

Serine/Threonine kinases

Ras pathway a

Binding

TK receptor phosphorylated

Grb2 activates SH2/3 domain

SH2/3 domains recruit Sos (GEF)

Ras activated and switches GDP to GTP

Ras pathway b

Binding

RTK phosphorylation

Shc and Grb2 recruit SH2/3 domain

SH2/3 domain recruits Sos (GEF)

Ras activated and switches GDP to GTP

MAP Kinase Pathway

Second Messenger Signaling

PI to PIP2 to PLC to IP3

OR

PI to PIP2 to PI3K to PIP3

what does PI3K do

Forward reaction PIP2 to PIP3

What does PTEN do

Reverse reaction PIP3 to PIP2

GSK-3B function

Proliferation

HIF-1a function

Angiogenesis

Bad function

Apoptosis

Cytokine JAK Stat pathway

Binding of hormone leads to receptor dimerization

JAKs auto-phosphorylate then cross-phosphorylate receptor tyrosines

Stats bind to the phosphorylated tyrosines

JAKs phosphorylate and activate Stats

Stats form dimers, then migrate and bind to DNA

Transcription genes are activated

Integrin receptor signaling

Link to ECM